Safety and Feasibility of Quantitative Multiplexed Cytokine Analysis From Office-Based Vitreous Aspiration.

PURPOSE: The goals of this study were to evaluate the safety of office-based vitreous sampling, and determine the utility of these samples with multiplex cytokine analysis. METHODS: Vitreous samples were collected from office-based needle aspiration and the rate of adverse events during follow-up was reviewed. The vitreous cytokine concentrations in a subset of patients with diabetic macular edema (DME) were analyzed using a 42 plex-cytokine bead array. These results were compared with vitreous cytokine concentrations in proliferative diabetic retinopathy (PDR) and controls (macular hole, epiretinal membrane, symptomatic vitreous floaters) from pars plana vitrectomy. RESULTS: An adequate volume of vitreous fluid (100-200 µL) was obtained in 52 (88%) of 59 office-based sampling attempts. The average length of follow-up was 300 days (range, 42-926 days). There were no complications, including cataract, retinal tear or detachment, and endophthalmitis. Two patients (3%) had posterior vitreous detachments within 3 months. Vitreous cytokine concentrations were measured in 44 patients: 14 controls, 13 with DME, and 17 with PDR. The concentration of ADAM11, CXCL-10, IL-8, and PDGF-A were higher in PDR compared with controls and DME. The concentration of IL-6 was higher in PDR compared with controls, but not compared with DME. CONCLUSIONS: Office-based vitreous aspiration is safe and yields high-quality samples for multiplex vitreous cytokine analysis. Significant elevations of vitreous cytokines were found in PDR compared with DME and controls, including the novel finding of elevated ADAM11. As such, office-based aspiration is a safe and effective means to identify vitreous factors associated with vitreoretinal disease.

PATHOGENESIS OF PERSISTENT PLACOID MACULOPATHY: A Multimodal Imaging Analysis.

PURPOSE: To describe previously unreported clinical characteristics of persistent placoid maculopathy, suggest a pathogenesis of persistent placoid maculopathy using multimodal imaging, and provide evidence supporting high-dose immunosuppression for short-term management. METHODS: Retrospective case series. RESULTS: The cohort included 3 men with ages ranging from 55 years to 68 years. Persistent placoid maculopathy was bilateral in all 3 patients and characterized by recurrence and choroidal neovascularization in 1 patient. The median time to presentation was 3 months (range, 2-24 months), and follow-up was 8 months (range, 3-24 months). Previously unreported findings of far-peripheral lesions and optic nerve hyperfluorescence on fluorescein angiography were noted in separate individuals. In addition, findings from multimodal imaging supported an inflammatory pathogenesis of the inner choroid and the outer retina. Finally, all patients experienced substantial improvement to structural and functional measures in at least one eye within days to weeks of initiating high-dose corticosteroids (0.75-1 mg/kg/day). CONCLUSION: Multimodal imaging suggests that persistent placoid maculopathy has an inflammatory pathogenesis that may affect the inner choroid with secondary changes to the retinal pigment epithelium and the outer retina. High-dose corticosteroids may provide short-term benefit.

Association between retinal nerve fiber layer thickness and abnormalities of vision in people with human immunodeficiency virus infection.

PURPOSE: To investigate relationships between contrast sensitivity (CS), color vision, and retinal nerve fiber layer (RNFL) among people with human immunodeficiency virus (HIV) infection; to evaluate the effect of time since diagnosis of HIV infection on RNFL thickness. DESIGN: Noninterventional cross-sectional study. METHODS: We evaluated 102 eyes of 57 HIV-infected individuals without ocular opportunistic infections. Peripapillary RNFL thickness was determined with spectral-domain optical coherence tomography in 4 quadrants. CS was measured with the Pelli-Robson technique (expressed as logCS); color vision was measured with the Lanthony desaturated 15-hue technique (expressed as color confusion index [C-index], with higher scores indicating worse color vision). Correlations between values were assessed using Spearman correlation coefficients. RESULTS: Median RNFL thickness (average of 4 quadrants) was 102.9 µm (range, 75.0-134.7 µm). Median logCS was 1.90 (range, 1.25-1.95). Median C-index was 1.58 (range, 0.96-4.07). Temporal RNFL thickness was correlated with logCS (r=0.295, P=.003) and C-index (r=-0.338, P=.0005). Time since diagnosis of HIV infection was shorter for those with thick average RNFL than for those with thin average RNFL (P=.18). CONCLUSIONS: Both worse CS and worse color vision are correlated with thinning of the temporal RNFL, with possible threshold effects. Increased prevalences of abnormal CS and abnormal color vision in this population are therefore likely attributable to neuroretinal compromise. This pattern of structural and functional losses may reflect preferential damage to small-caliber axons in the maculopapillary bundle, possibly associated with mitochondrial dysfunction, providing a potential disease mechanism for HIV-associated "neuroretinal disorder."

Retinal vessel caliber among people with acquired immunodeficiency syndrome: relationships with visual function.

PURPOSE: To evaluate relationships between retinal vessel caliber and tests of visual function among people with AIDS. DESIGN: Longitudinal, observational cohort study. METHODS: We evaluated data for participants without ocular opportunistic infections at initial examination (baseline) in the Longitudinal Studies of the Ocular Complications of AIDS (1998-2008). Visual function was evaluated with best-corrected visual acuity, Goldmann perimetry, automated perimetry (Humphrey Field Analyzer), and contrast sensitivity (CS) testing. Semi-automated grading of fundus photographs (1 eye/participant) determined central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) at baseline. Multiple linear regression models, using forward selection, sought independent relationships between indices and visual function variables. RESULTS: Included were 1250 participants. Smaller AVR was associated with reduced visual field by Goldmann perimetry (P = .003) and worse mean deviation (P = .02) on automated perimetry and possibly with worse pattern standard deviation (PSD) on automated perimetry (P = .06). There was a weak association between smaller AVR and worse CS (P = .07). Relationships were independent of antiretroviral therapy and level of immunodeficiency (CD4+ T lymphocyte count, human immunodeficiency virus [HIV] RNA blood level). On longitudinal analysis, retinal vascular indices at baseline did not predict changes in visual function. CONCLUSIONS: Variation in retinal vascular indices is associated with abnormal visual function in people with AIDS, manifested by visual field loss and possibly by reduced CS. Relationships are consistent with the hypothesis that HIV-related retinal vasculopathy is a contributing factor to vision dysfunction among HIV-infected individuals. Longitudinal studies are needed to determine whether changes in indices predict change in visual function.

Retinal vessel caliber among people with acquired immunodeficiency syndrome: relationships with disease-associated factors and mortality.

PURPOSE: To evaluate relationships between retinal vessel caliber, AIDS-related factors, and mortality. DESIGN: Longitudinal, observational cohort study. METHODS: We evaluated data for participants without ocular opportunistic infections at initial examination (baseline) in the Longitudinal Studies of the Ocular Complications of AIDS (1998-2008). Semi-automated evaluation of fundus photographs (1 eye/participant) determined central retinal artery equivalent (CRAE), central retinal vein equivalent (CRVE), and arteriole-to-venule ratio (AVR) at baseline. Multiple linear regression models, using forward selection, identified independent relationships between indices and various host- and disease-related variables. RESULTS: Included were 1250 participants. Mean follow-up for determination of mortality was 6.1 years. Smaller CRAE was related to increased age (P < .001) and hypertension (P < .001); larger CRAE was related to lower hematocrit (P = .002). Larger CRAE and CRVE were associated with black race (P < .001). Larger CRVE was related to smoking (P = .004); smaller CRVE was related to age (P < .001) and higher mean corpuscular volume (P = .001). We observed the following relationships with AIDS-associated factors: smaller CRAE and larger CRVE with history of highly active antiretroviral therapy (HAART; P < .001); and larger CRAE with lower CD4+ T lymphocyte count (P = .04). We did not identify independent relationships with human immunodeficiency virus RNA blood levels. There was a 12% (95% CI, 2%-21%) increase in mortality risk per quartile of decreasing AVR (P = .02). CONCLUSIONS: Variations in retinal vascular caliber are associated with AIDS-specific factors and are markers for increased mortality risk. Relationships are consistent with the hypothesis that the vasculature is altered by known atherogenic effects of chronic HAART or the prolonged inflammatory state associated with AIDS.

Accuracy and reliability of telemedicine for diagnosis of cytomegalovirus retinitis.

PURPOSE: To determine the feasibility of remote diagnostic screening for cytomegalovirus (CMV) retinitis among HIV patients in northern Thailand. DESIGN: Prospective, observational cross-sectional study. METHODS: One hundred eighty-two eyes from 94 consecutive patients with HIV seen in 2008 and 2009 at a tertiary university-based medical center were photographed using a digital retinal camera. Individual and composite images were uploaded to a secure web site. Three expert graders accessed the electronic images and graded each image for signs of CMV retinitis. Results of remote expert grading were compared with on-site patient examination by local expert ophthalmologists. RESULTS: On-site ophthalmologists diagnosed CMV retinitis in 89 (48.9%) of 182 eyes. Trained ophthalmic photographers obtained digital retinal images for all 182 eyes. As compared with the on-site examinations, the sensitivity for detecting CMV retinitis by remote readers using composite retinal images ranged from 89% to 91%. The specificity for detecting CMV retinitis by remote readers ranged from 85% to 88%. Intrarater reliability was high, with each grader achieving a κ value of 0.93. Interrater reliability among the 3 graders also was high, with a κ value of 0.86. CONCLUSIONS: Remote diagnostic screening for CMV retinitis among HIV-positive patients may prove to be a valuable tool in countries where the burden of HIV exceeds the capacity of the local eye care providers to screen for ocular opportunistic infections.